Throughout the graduate and postdoctoral stages, my goal has been to get training and experience that will allow me to establish an independent and successful research program in developmental and cancer biology. Specifically, I am interest in the mechanisms that regulate epithelial tissue development and homeostasis, and to changes that occur in disease states such as cancer. My plan for the reminder of the postdoctoral training is to acquire additional skills and develop research material that I will be able to carry into an independent position in academia. The Rockefeller University is an ideal place for the development of my career as an independent researcher. The University is a part of the Tri-Institutional Program, together with Memorial Sloan-Kettering Cancer Center and Weill-Cornell Medical College, which is a premier environment to conduct research, interact with fellow scientists, and attend lectures by leaders in a variety of fields. The Tri-Institutional group also organizes workshops in bioinformatics and biostatistics, and lectures dedicated to clinical and cancer research, both of which are the focus of my training. Furthermore, here I will interact with collaborators that are experts in computational and cancer biology. Lastly, the resources within the Fuchs laboratory and the Resource Centers present at the Rockefeller University will provide equipment, training, and technical help that will ensure successful completion of the proposed research. In order to meet my research and career development goals I propose to conduct a genome-wide, RNAi- mediated modifier screen in vivo, to uncover regulatory mechanisms that govern epidermal tissue growth and homeostasis during development and in oncogene-induced hyperplasia. I expect that this comprehensive work will result in identification of many candidate genes that specifically operate within the physiological environment. The high-throughput nature and the originality of the approach that I propose, will allow me to complete postdoctoral training, and in the process set up a solid foundation for the future research program. At the start of the independent stage, I will base my research on identifying mechanisms used by selected candidates, to regulate tissue growth in the models of embryonic skin development and epidermal tumorigenesis. I will use these findings in subsequent grant support applications to the NIH (NIAMS and NCI), and other available sources of funding. PUBLIC HEALTH RELEVANCE: What a cell does, during normal organ development or in a complex disease like cancer, is defined by its intrinsic potential and by instructions that it receives from the physiological environment. To date, we have been successful in identifying regulators of cell autonomous behaviors, but the environmental influences have been harder to study. This proposal aims to take advantage of recent technical progress, and conduct a comprehensive, genome-wide investigation of the effect of environmental input on tissue growth during development and cancer.